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Title: XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells.
Author: Moreno-Martínez, Daniel
Nomdedeu i Fàbrega, Meritxell
Lara Castillo, María Carmen
Etxabe, Amaia
Pratcorona, Marta
Tesi, Niccolò
Díaz-Beyá, Marina
Rozman, María
Montserrat Costa, Emilio
Urbano Ispizua, Álvaro
Esteve, Jordi
Risueño, Ruth M.
Keywords: Leucèmia mieloide
Cèl·lules mare
Myeloid leukemia
Stem cells
Issue Date: 30-Jun-2014
Publisher: Impact Journals
Abstract: Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2014, vol. 5, num. 12, p. 4337-4346
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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